Activation of the complement (C') system, with ceneration of inflammatory mediators and membrane attack complexes (C5-9) is implicated in the pathogenesis of the inflammation and bone resorption in periodontitis. Previous work on C'membrane interaction employed non-nucleated cells or liposomes. In inflammation, however, it is often the nucleated cell which interacts with activated C' proteins. This proposal is to study the interaction of C5-9 with nucleated cell membranes. Since nucleated cells can synthesize and repair complex membrane, their interaction with C' could differ from that of erythrocytes. Specifically we want to determine: 1) whether C' mediated cell death exhibits single hit or multi hit kinetics 2) whether the C' channel is stable in the nucleated cell membrane 3) whether agents which alter complex lipid synthesis of nucleated cells affect c' interaction with these cells. MOLT-4 cells will be used as nucleated cell targets. Activation of c' will be accomplisheds by specific antibody as well as by reactive lysis with C5b6-C9. The kinetics of cell lysis will be determined by classic C' titration experiments with a limiting single component in the presense of excess others. Stability of the C' lesions in the membrane will be assessed by establishing stable intermediate C7 and C8 sites on the nucleated membrane over a varied time course. Titration of the residuel sites will be done by the addition of the terminal components required for lysis. An I125 labelled C5 will be used to trace the membrane associated C' components. Finally adriamycin and steroids will be used in an attempt to alter nucleated cell interaction with C' lesions. These studies will provide basic information on nucleated cell responses to C' attack during inflammation that would help to interpret the role of C' in membrane modulation and cell death.